Tissue acidosis may contribute to pain associated with tissue injury or inflammation. Studies have demonstrated that application of acidic solutions to human skin produced graded tissue acidosis and sustained burning pain. Recently, the frog has been proposed as an alternative animal model for pain. A drop of acetic acid (AA) applied to hindlimb skin results in nociceptive behaviors, including a quick wiping of the exposed skin. However, whether the nociceptive behaviors are evoked by decreased tissue pH produced by acetic acid is unknown. Therefore, the first specific aim of these experiments is to determine if the acidity of acetic acid (or another characteristics such as osmolarity) is important for evoking the nociceptive behaviors. Additionally, little is known about the cutaneous receptors in frogs that respond to AA. Thus, the second specific aim of these experiments is to characterize frog cutaneous receptors, particularly those responsive to AA. Our long term goal is to elucid ate the role of tissue acidosis in painful conditions. Such study may suggest novel therapeutic approaches for pain associated with tissue injury or inflammation. To complete the first specific aim, parallel behavioral and subepithelial pH measurement experiments will be performed to determine which characteristics of acetic acid are important for evoking the nociceptive behaviors. To complete the second specific aim, extracellular electrophysiological recordings will be made from the dorsal roots and spinal nerves innervating the skin of the hindlimb. The receptive fields of these primary afferents will be characterized by their conduction velocities and their responses to mechanical, themal, and chemical stimuli. The responses to acetic acid will.be compared to the results from the behavioral and subepithelial pH measurement experiments. These comparisons should reveal which classes of cutaneous receptors likely underlie the wiping response in this model of nociception. By comparing the characteristics of frog receptors responsive to AA with those of acid-sensitive cutaneous receptors reported in mammalian skin, the validity of the frog model of acidotic pain can be determined. Key Words: tissue acidosis, nociceptors, primary afferents, electrophysiology, pH measurements, frogs